The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology

Abstract

Adolescent exposure to cannabinoids as a postnatal environmental insult may increase the risk of psychosis in subjects exposed to perinatal insult, as suggested by the two-hit hypothesis of schizophrenia. Here, we hypothesized that peripubertal Δ9-tetrahydrocannabinol (aTHC) may affect the impact of prenatal methylazoxymethanol acetate (MAM) or perinatal THC (pTHC) exposure in adult rats. We found that MAM and pTHC-exposed rats, when compared to the control group (CNT), were characterized by adult phenotype relevant to schizophrenia, including social withdrawal and cognitive impairment, as revealed by social interaction test and novel object recognition test, respectively. At the molecular level, we observed an increase in cannabinoid CB1 receptor (Cnr1) and/or dopamine D2/D3 receptor (Drd2, Drd3) gene expression in the prefrontal cortex of adult MAM or pTHC-exposed rats, which we attributed to changes in DNA methylation at key regulatory gene regions. Interestingly, aTHC treatment significantly impaired social behavior, but not cognitive performance in CNT groups. In pTHC rats, aTHC did not exacerbate the altered phenotype nor dopaminergic signaling, while it reversed cognitive deficit in MAM rats by modulating Drd2 and Drd3 gene expression. In conclusion, our results suggest that the effects of peripubertal THC exposure may depend on individual differences related to dopaminergic neurotransmission.

Olanzapine, but not haloperidol, exerts pronounced acute metabolic effects in the methylazoxymethanol rat model

“…They were randomly assigned to saline‐treated group (control group – CTR) or methylazoxymethanol acetate‐treated group (MAM). The MAM model was induced as previously described and validated 44–50 . Briefly, MAM was dissolved in saline and intraperitoneally administered at a dose of 22 mg/kg in 1 mL/kg volume on GD 17.…”

“…The MAM model was induced as previously described and validated. [44][45][46][47][48][49][50] Briefly, MAM was dissolved in saline and intraperitoneally administered at a dose of 22 mg/kg in 1 mL/kg volume on GD 17. The offspring were weaned on a postnatal day (PND) 22 and housed in groups of 2-3.…”

Cannabis and sport: A World Anti‐Doping perspective

“…Chronic, frequent use of cannabis is associated with an increased risk of cannabis use disorder, as recently reviewed by Robinson and colleagues [13], as well as potentially other long-term changes [14,15], including an increased risk of precipitation of severe mental illness [16]. There is a growing body of evidence that cannabis use can affect brain development and anatomy in adolescents and young adults [17][18][19], although the consequences of these changes are not yet firmly established. The potential of cannabis use to compromise the health and safety of the athlete qualifies the application of this criterion.…”